Elephant Black Garlic's Beneficial Properties for Hippocampal Neuronal Network, Chemical Characterization and Biological Evaluation.

Garlic has been used for decades as an important food and additionally for its beneficial properties in terms of nutrition and ancestral therapeutics. In this work, we compare the properties of fresh (WG) and aged (BG) extract obtained from elephant garlic, harvested on Chiloe Island, Chile. BG was prepared from WG with a 20-day aging process under controlled temperature and humidity conditions. We observed that in BG, compounds such as diallyl disulfide decrease, and compounds of interest such as 5-hydroxymethylfurfural (69%), diallyl sulfide (17%), 3H-1,2-Dithiole (22%) and 4-Methyl-1,2,3-trithiolane (16%) were shown to be increased. Using 2,2-diphenyl-1-picrylhydrazyl (DPPH, BG: 51 ± 5.7%, WG: 12 ± 2.6%) and 2,20-azino-bis-(3-ethylbenzothiazoline-6 sulfonate) diammonium salt (ABTS, BG: 69.4 ± 2.3%, WG: 21 ± 3.9%) assays, we observed that BG possesses significantly higher antioxidant activity than WG and increased cell viability in hippocampal slices (41 ± 9%). The effects of WG and BG were shown to improve the neuronal function through an increased in intracellular calcium transients (189 ± 4%). In parallel, BG induced an increase in synaptic vesicle protein 2 (SV-2; 75 ± 12%) and brain-derived neurotrophic factor (BDNF; 32 ± 12%) levels. Thus, our study provides the initial scientific bases to foster the use of BG from Chiloe Island as a functional food containing a mixture of bioactive compounds that may contribute to brain health and well-being.

17 Oxo Sparteine and Lupanine, Obtained from Cytisus scoparius, Exert a Neuroprotection against Soluble Oligomers of Amyloid-ß Toxicity by Nicotinic Acetylcholine Receptors.

Alzheimer's disease (AD) is a neurodegenerative pathology, which is characterized by progressive and irreversible cognitive impairment. Most of the neuronal perturbations described in AD can be associated with soluble amyloid- ß oligomers (SO-Aß). There is a large amount of evidence demonstrating the neuroprotective effect of Nicotine neurotransmission in AD, mainly through nicotinic acetylcholine receptor (nAChR) activation and antiapoptotic PI3K/Akt/Bcl-2 pathway signaling. Using HPLC and GC/MS, we isolated and characterized two alkaloids obtained from C. scoparius, Lupanine (Lup), and 17- oxo-sparteine (17- ox), and examined their neuroprotective properties in a cellular model of SO-Aß toxicity. Our results showed that Lup and 17- ox (both at 0.03µM) prevented SO-Aß-induced toxicity in PC12 cells (Lup: 64±7%; 17- ox: 57±6%). Similar results were seen in hippocampal neurons where these alkaloids prevented SO-Aß neurotoxicity (Lup: 57±2%; 17- ox: 52±3%) and increased the frequency of spontaneous calcium transients (Lup: 60±4%; 17- Ox: 40±3%), suggesting an enhancing effect on neural network activity and synaptic activity potentiation. All of the neuroprotective effects elicited by both alkaloids were completely blocked by α-bungarotoxin. Additionally, we observed that the presence of both Lup and 17- ox increased Akt phosphorylation levels (52±4% and 35±7%, respectively) in cells treated with SO-Aß (3 h). Taken together, our results suggest that the activation of nAChR by Lup and 17- ox induces neuroprotection in different cellular models, and appears to be an interesting target for the development of new pharmacological tools and strategies against AD.

A Natural Benzofuran from the Patagonic Aleurodiscus vitellinus Fungus has Potent Neuroprotective Properties on a Cellular Model of Amyloid-ß Peptide Toxicity.

Alzheimer's disease (AD) is characterized by amyloid plaques that form due to an increase in amyloid-ß peptide (Aß) aggregation. One strategy in the search of new treatments for AD focuses on compounds that decrease Aß accumulation. Compounds containing a benzofuran ring have been described to play an important role in decreasing Aß-induced toxicity; however, only synthetic benzofurans have been tested thus far. The aim of the present study was to examine the in vitro neuroprotective properties of fomannoxin (Fx), a natural benzofuran isolated from cultures of the Andean-Patagonian fungi Aleurodiscus vitellinus, and evaluate its effect on Aß peptide. We tested the effect of Fx at a wide concentration range (10-11-10-4 M) in PC-12 cells, and found the compound did not alter cellular viability. Fx also showed a concentration-dependent effect on the Aß-induced toxicity in PC12 cells, showing viability above 100% at 10-6 M. We then measured the effect of Fx (10-7-10-5 M) on the frequency of cytosolic Ca2+ transients in rat hippocampal neurons at both acute and chronic (24 h) times. Acute incubation with Fx increased the frequency of cytosolic Ca2+ transients to values around 200%, whereas chronic incubation with Fx increased the frequency of Ca2+ transients. Finally, the Aß-induced decrease in intracellular Ca2+ transients was prevented when Fx (10-6 M) was co-incubated with Aß (5×10-6 M). The results suggest a potent neuroprotective effect of this naturally occurring benzofuran against Aß peptide toxicity that could be mediated by an interference with it binding to plasma membrane, and lead Fx as new chemical entity to develop pharmacological tools against Aß peptide neurotoxicity.

Retinoblastoma en pediatría, experiencia en un hospital pediátrico / Retinoblastoma in children, experience at a pediatric hospital

Methods: Retrospective analysis of clinical charts of 41 children (59 eyes) diagnosed with retinoblastoma and treated by a multidisciplinary team at Hospital Luis Calvo Mackenna in Santiago-Chile, between 1999 and 2007. The information included gender, laterality, diagnosis age, presenting signs, tumor spread, treatment modality and survival rate. Results: A total of 23 cases (56 percent) were unilateral and 18 cases (44 percent) were bilateral. The mean age at diagnosis was 21.6 months (range 2 - 84) and 27 children (65.9 percent) were male. The most common presenting signs were leucokoria (51.2 percent), strabismus (24.4 percent) and proptosis (4.9 percent). Enucleation was performed in 48 eyes (81.3 percent), being the only required treatment in 17 children (41.5 percent). The remaining 24 patients received systemic and/or local therapy with chemotherapy, focal therapy and external beam radiation. 5 children died during the follow - up study period, due to extraocular extension to the orbit, central nervous system and bone marrow. Conclusion: In spite of high enucleation rate as initial therapy for retinoblastoma, the survival rate with this current treatment protocol is similar to those from developed countries.

Se presenta un estudio retrospectivo de las fichas clínicas de 41 niños (59 ojos) con diagnóstico de retinoblastoma tratados por un equipo multidisciplinario en el Hospital Luis Calvo Mackenna, Santiago, Chile, entre los a±os 1999-2007. Se recolectó información respecto al género, edad al diagnóstico, signos de presentación, lateralidad, diseminación del tumor, tipos de tratamiento y sobrevida. Veintitrés casos (56 por ciento) fueron unilaterales y 18 (44 por ciento) bilaterales. La edad promedio al momento del diagnóstico fue de 21,6 meses (rango 2-84) y 27 niños (65,9 por ciento) fueron hombres. Los signos de presentación más frecuentes fueron leucocoria (51,2 por ciento), estrabismo (24,4 por ciento) y proptosis (4,9 por ciento). Se realizó enucleación en 48 ojos afectados (81,3 por ciento), siendo el único tratamiento necesario en 17 niños (41,5 por ciento). Los 24 pacientes restantes recibieron tratamientos complementarios locales y/o sistémicos en la modalidad de quimioterapia, terapia focal y radioterapia externa. Durante el período de seguimiento del estudio fallecieron 5 niños, todos ellos con extensión extraocular de la enfermedad hacia la órbita, sistema nervioso central o médula ósea. Conclusiones: No obstante el alto porcentaje de pacientes con retinoblastoma que requieren enucleación como terapia inicial, la tasa de sobrevida con el protocolo actual de tratamiento es comparable a la de países desarrollados.